Harry A. Oberhelman

Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas

Only 10% to 20% of patients with pancreatic cancer are considered candidates for curative resection at the time of diagnosis. We postulated that preoperative chemoradiation therapy might promote tumor regression, eradicate nodal metastases, and allow for definitive surgical resection in marginally resectable patients. The objective of this study was to evaluate the effect of a preoperative chemoradiation therapy regimen on tumor response, resectability, and local control among patients with marginally resectable adenocarcinoma of the pancreas and to report potential treatment-related toxicity. Patients with marginally resectable adenocarcinoma of the pancreas (defined as portal vein, superior mesenteric vein, or artery involvement) were eligible for this protocol. Patients received 50.4 to 56 Gy in 1.8 to 2.0 Gy/day fractions with concurrent protracted venous infusion of S-fluorouracil (250 mg/m2/day). Reevaluation for surgical resection occurred 4 to 6 weeks after therapy. Fifteen patients (9 men and 6 women) completed preoperative chemoradiation without interruption. One patient required a reduction in the dosage of S-fluorouracil because of stomatitis. Acute toxicity from chemoradiation consisted of grade 1 or 2 nausea, vomiting, diarrhea, stomatitis, palmar and plantar erythrodysesthesia, and hematologic suppression. CA 19-9 levels declined in all nine of the patients with elevated pretreatment levels. Nine of the 1.5 patients underwent a pancreaticoduodenectomy, and all had uninvolved surgical margins. Two of these patients had a complete pathologic response, and two had microscopic involvement of a single lymph node. With a median follow-up of 30 months, the median survival for resected patients was 30 months, whereas in the unresected group median survival was 8 months. Six of the nine patients who underwent resection remain alive and disease free with follow-up of 12, 30, 30, 34, 39, and 72 months, respectively. Preoperative chemoradiation therapy is well tolerated. It may downstage tumors, sterilize regional lymph nodes, and improve resectability in patients with marginally resectable pancreatic cancer. Greater patient accrual and longer follow-up are needed to more accurately assess its future role in therapy.

Adjuvant radiotherapy and concomitant 5-fluorouracil by protracted venous infusion for resected pancreatic cancer

PURPOSE To assess the toxicity and clinical benefit from adjuvant chemoradiotherapy consisting of protracted venous infusion 5-fluorouracil (5-FU) and concomitant radiotherapy in patients with resected pancreatic cancer. METHODS AND MATERIALS Between 1994 and 1999, 52 patients who underwent pancreaticoduodenectomy received adjuvant chemoradiotherapy. The tumor bed and regional nodes received a dose of 45 Gy in fractions of 1.8 Gy followed by boost to the tumor bed if the surgical margins were involved (total dose, 54 Gy). The patients also received concomitant 5-FU by protracted venous infusion (200-250 mg/m(2)/day, 7 days/week) during the entire radiotherapy course. RESULTS Fifty-two patients (30 men, 22 women) were enrolled and treated on this protocol. The median age was 63 years (range, 38-78 years), and the median Karnofsky Performance Status was 80 (range, 70-100). Thirty-five percent had involved surgical margins and 59% had involved lymph nodes. All patients completed therapy, and there were no Grade IV/V toxicities observed. With median follow-up of 24 months (range, 3-52 months) for surviving patients, the median survival is 32 months, and 2-year and 3-year survivals are 62%, and 39%, respectively. CONCLUSION Radiotherapy with concomitant 5-FU by protracted venous infusion as adjuvant treatment for resected pancreatic cancer is well tolerated. This approach allows for greater dose intensity with reduced toxicity. The median survival of this cohort of patients compares favorably with our earlier experience and other published series.

Diverting ileostomy in the surgical management of Crohn's disease of the colon.

Abstract Diverting ileostomy has been performed in thirteen patients with Crohns disease of the colon with or without ileal involvement. Immediate and persistent relief of symptoms has occurred in all patients in three to twenty-four months (mean sixteen months) without evidence of recurrence. Radiologic as well as histologic findings have shown a return towards normal. Three patients have undergone restoration of intestinal continuity after two years. A mild recurrence developed in one patient which was controlled by corticosteroids whereas the other two remain well after two and thirty-six months. The results of diverting ileostomy have been unsuccessful in cases of chronic ulcerative colitis, further serving to illuminate fundamental differences in addition to clinical and histologic differences between these two inflammatory conditions. Further experience with this mode of therapy is justified.

Protracted venous infusion 5-fluorouracil with concomitant radiotherapy compared with bolus 5-fluorouracil for unresectable pancreatic cancer.

Radiation therapy (RT) with concurrent 5-fluorouracil (5-FU) administered by protracted venous infusion (PVI) replaced our prior institutional protocol of RT with bolus administration of 5-FU as standard therapy for unresectable pancreatic cancer in 1994. In this article, we compare the treatment intensity, toxicity, and outcome for patients with unresectable pancreatic cancer treated on these sequential protocols. Fifty-four patients, 27 on each protocol, with biopsy-confirmed pancreatic cancer received chemoradiotherapy. The radiotherapy field included the gross tumor volume and regional lymph nodes to a dose of 45 Gy, followed by “boost” to the gross tumor volume to 54 Gy to 60 Gy. From 1987 to 1994, patients received concurrent 5-FU administered by bolus injection, at a dose of 500 mg/m2 on days 1 to 3 and days 29 to 31 of RT. After December 1994, 5-FU was administered by PVI (200–250 mg/m2) beginning on day 1 and continuing until the completion of RT. The chemotherapy treatment intensity was increased in the group receiving 5-FU by PVI, as evidenced by an increased average weekly and cumulative dose of 5-FU (p < 0.01). The radiotherapy treatment intensity was equivalent between the two groups. The incidence of objectively quantified toxicity was not statistically different between treatment groups. Overall survival remained poor in both treatment groups. With a median follow-up of 18 months (range: 3–30 months) for surviving patients, the 6-month, 1-year, and 2-year survivals for the PVI 5-FU-treated group versus the bolus 5-FU-treated group were 56% versus 52%, 34% versus 18%, and 22% versus 13%, respectively (p = 0.9). Radiotherapy with concomitant 5-FU by PVI results in a greater weekly and total dose of chemotherapy. The method of 5-FU administration (bolus versus PVI) did not change the RT treatment intensity, experienced toxicity, or overall survival.

Significance of innervation in the function of the gastric antrum.

The antrum of the stomach in dogs was excluded by constructing a membrane of gastric mucosa separating the cavity of the antrum from that of the corpus. A fistula was made of the pylorus and intest...

Combined treatment of cancer of the esophagus

Abstract Forty patients with carcinoma of the thoracic esophagus were entered into a treatment plan utilizing megavoltage radiation therapy and excision of the entire thoracic esophagus. No patient with advanced primary disease or metastasis to the regional lymphatics benefited from this plan of treatment. Three patients are alive and without disease, nine, thirty-six, and sixty-two months after surgery, respectively.

Antrum Motility as a Stimulus for Gastric Secretion

Summary Observations have been recorded concerning the effects of various procedures such as removal of vagus innervation, transplantation of the antrum to the abdominal wall and into the colon, on the total output of gastric juice from a Pavlov pouch. It is concluded that the hormonal or antrum phase of gastric secretion is most important, the nervous phase of secretion is somewhat less, and the intestinal phase is least important in provoking the secretion of gastric juice from a Pavlov accessory stomach pouch. The antrum of the stomach, transplanted into the colon, causes a greater secretion of gastric juice than is produced when the antrum is in its normal location. This secretion may continue even though the original blood supply to the antrum is divided, and it is nourished by newly formed blood vessels from the colon. In the absence of other factors, the development of pressure within the isolated colon containing an antrum transplant as a result of peristalsis is a profound stimulation for antrum function. The significance of this finding as a possible explanation for the increase in gastric secretion accompanying pyloric stenosis in man is suggested.

RESPONSE TO BYPASS ILEOSTOMY IN ULCERATIVE COLITIS AND CROHN'S DISEASE OF THE COLON

Abstract Ileostomy, excluding intestinal contents from the colon, was done in sixteen patients with chronic inflammatory disease of the large intestine. Ten patients had Crohns disease, five had ulcerative colitis, and one could not be classified. These designations were based on histological assessment. Clinical recovery followed operation in the Crohns disease group; the only relapse to occur was in one of the two patients who had intestinal continuity restored. In the ulcerative colitis group, on the other hand, relapse was universal; four of the five patients required total colectomy. The response to bypass ileostomy suggests that there is a fundamental difference between ulcerative colitis and Crohns disease.

Surgical management of peptic ulcer

Abstract I have attempted to review briefly my philosophy to the surgical approach of peptic ulcer based on the many important physiologic observations that have emerged over the years. Only by such an approach can we as surgeons improve the results of operative therapy, not only in terms of its effectiveness in preventing recurrent ulceration but also in reducing mortality and morbidity to the lowest degree possible. It is obvious that further advances are yet to be made in all these areas, improvements that will continue to further the health of patients afflicted with this disease.

Diverting ileostomy for colonic Crohn's disease part I: Significance of ulcers 5 mm in depth or deeper on the preoperative barium enema

In patients with colonic Crohns disease who had failed to respond to medical treatment, a diverting ileostomy resulted in persistent relief of symptoms in 60% of the cases. The authors reviewed the radiographs performed prior to diverting ileostomy on 15 patients who had colonic Crohns disease. A number of spike-like ulcers in the colon, 5 mm in depth or deeper, of various types, occurred in patients in whom surgery had failed. Ulcers 5 mm or greater in depth destroy the colonic muscularis propria and, if numerous, probably result in irreversible changes. If studies on larger numbers of patients confirm this finding, diverting ileostomy would be indicated before numerous deep ulcers develop.